The findings of our work suggest that at least some of these features are general to viral RdRps and provide further details on the original nucleotide selection mechanism operating in RdRps of RNA viruses. These dynamics are finely regulated by a second magnesium dication, thus coordinating the entry of a magnesium-bound nucleotide with shuttling of the second magnesium necessary for the two-metal ion catalysis. Dynamics of RdRp motifs F1 + F3 then allow the nucleotide to interrogate the RNA template base prior to nucleotide insertion into the active site. We observed that a magnesium-bound nucleotide first binds next to the tunnel entry, and interactions with the triphosphate moiety orient it such that its base moiety enters first. Tracing the possible passage of incoming UTP or GTP through the RdRp-specific entry tunnel, we found two successive checkpoints that regulate nucleotide traffic to the active site. ![]() Here, we used molecular modeling and molecular dynamics simulations, starting from the available crystal structures of HCV NS5B in ternary complex with template-primer duplexes and nucleotides, to address the question of ribonucleotide entry into the active site of viral RdRp. However, peculiarities in the architecture and dynamics of RdRps raise fundamental questions about access to their active site during RNA polymerization. As such, these enzymes are prime targets for antiviral therapy, as has recently been demonstrated for hepatitis C virus (HCV). In early April 2021, the still image from bradeazy's "Trade Offer" video has been widely used as an exploitable and source material for redraws.RNA viruses synthesize new genomes in the infected host thanks to dedicated, virally-encoded RNA-dependent RNA polymerases (RdRps). On April 2nd, 2021, Redditor Cryoffe posted a meme that gained over 17,000 upvotes in the /r/196 subreddit in four days (shown below, right). On March 29th, an unknown user posted a Team Fortress 2 version of the meme that was widely circulated online in the following days (shown below, left). The format did not achieve pronounced popularity until late March 2021 when bradeazy's first video and a still image from it received viral spread. On March 18th, iFunny user Buffchicks_likedick posted the earliest derivative meme based on the video, altering the caption to include "A Bionicals lego Set." The post gained over 320 smiles (shown below). Between March 18th and April 3rd, 2021, bradeazy posted four additional memes using the format on TikTok. On March 18th, bradeazy reposted the video to his Instagram account where it gained over 11,000 likes (also unavailable).Īlso on March 18th, iFunny user ChipSkylark reposted the video to the app, where it gained over 42,100 smiles after being featured. Prior to March 18th, 2021, TikTok user bradeazy posted a version of the meme in which he, dressed in formal wear, offered nothing in exchange for a "sloppy toppy" (the original TikTok is no longer available). On March 8th and 9th, TikTokers schmuellersvibechamber, macncheesegrrl and jushlarsen posted some of the earliest versions of the meme, gaining over 461,000, 295,000 and 1 million views, respectively (shown below). ![]() In the following days, the format gained a significant presence on TikTok with multiple viral examples of the meme posted in mid-March 2021. The video received over 440,000 views and 66,100 likes in one month (shown below). On March 8th, TikTok user tylertctv posted a video in which he proposed a trade offer to God. The video did not spark a trend until March 2021. The TikTok received over 683,700 likes and 86,800 likes in five months (shown below). On November 12th, 2020, TikTok user posted a video that used a jingle played during the 2020 NBA draft, captioning the video "Trade proposal to God" and offering on behalf of humanity to swap several living people for several dead.
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